Novel multi-level intervention strategies are needed to combat the burgeoning pandemics of diabetes, obesity and their related comorbidities among highly impacted populations. Neighborhood environments and Latino health have only been studied in one large cohort study to date, The Multi Ethnic Study of Atherosclerosis. We propose a cost-effective ancillary study, submitted in response to PAR-13-302, that leverages existing data from the Hispanic Community Health Study - Study of Latinos (HCHS-SOL), while adding comprehensive neighborhood environment assessments and Visit 2 physical activity assessments to this ongoing cohort study. The proposed study is timely because the rapidly growing Latino population, particularly Mexican Americans, experience disproportionally high rates of cardiometabloic diseases such as diabetes and obesity. In this study we will investigate neighborhood environment impacts on cardiometabolic health in the HCHS/SOL San Diego cohort (N = 1750 Mexican Americans) using an innovative and comprehensive Social-Ecological Model that considers multiple pathways linking both macro- and micro-scale built and social neighborhood factors to cardiometabolic health using a longitudinal framework. Six year trajectories in cardiometabolic outcomes will be derived from comprehensive clinical assessments during 2008-2011 (Visit 1) and 2015-2018 (Visit 2). Physical activity was/will be assessed at Visits 1 and 2 using accelerometry and validated self-report. Chronic stress and social support will be assessed using validated self-reports at Visit 2, while depression was/will be assessed at both visits. Macro-scale neighborhood attributes (e.g., residential density, median household income) will be derived from GIS and public source data such as the American Community Survey using 1km street-network buffers around participants' homes. Micro-scale attributes (e.g., safety of street crossings, aesthetics/social disorder) will be assessed using systematic direct observations of participants' neighborhoods. Both cross-sectional and longitudinal structural equation models will be used to investigate direct and indirect (through physical activity, depression, chronic stress, and social support) effects of neighborhood environments on a cardiometabolic composite score comprised of the Metabolic Syndrome components (i.e., waist circumference, systolic blood pressure, HDL-cholesterol, fasting glucose and fasting triglycerides). As posited in Social-Ecological Models, we powered this study to test mediation (through the aforementioned behavioral and psychosocial pathways) and interactions among neighborhood attributes (e.g., built and social). By improving understanding of neighborhood effects on Latino health, this project will inform health-supportive neighborhood interventions in high-need areas, as well as behavioral and psychosocial interventions to minimize the negative health impacts of unsupportive neighborhood environments.